Subjects

BACKGROUND: Pre-exposure prophylaxis is becoming a strategic component used to control the human immunodeficiency virus (HIV-1) epidemic. The goal of this study was to characterize intracellular uptake of tenofovir and emtricitabine using five surrogate cell lines of the female genital tract and determine whether exogenous hormones influence their uptake.
METHODS: Surrogate cell lines, ie, THP-1 (representing macrophages), BC-3 (CD8+), Ect1/E6E7 (squamous epithelial), HeLa (CD4+), and TF-1 (dendritic), were incubated for one hour with tenofovir and emtricitabine to assess uptake. In separate experiments, ethinyl estradiol (EE) and etonogestrel (ET) individually and together (EE/ET) were added prior to, simultaneously, and after incubation. Intracellular phosphorylated tenofovir and emtricitabine were quantified using validated tandem mass spectrometry methods.
RESULTS: HeLa and Ect1/E6E7 cells showed significantly increased uptake relative to THP-1 controls for both antiretrovirals. Individually, ethinyl estradiol and etonogestrel significantly altered antiretroviral uptake across all cell lines, except Ect1/E6E7 for tenofovir and HeLa for emtricitabine. Cellular uptake of tenofovir and emtricitabine in BC-3 and TF-1 cells were significantly lower when dosed one hour prior to EE/ET administration compared with each antiretroviral administered in the absence of EE/ET (tenofovir, 80 versus 470 fmol/10(6) for BC-3 and 77 versus 506 fmol/10(6) cells for TF-1; emtricitabine, 36 versus 12 fmol/10(6) for BC-3 and 75 versus 5 fmol/10(6) cells for TF-1; P < 0.01 for each).
CONCLUSION: These data suggest that intracellular uptake of tenofovir and emtricitabine within the female genital tract varies by cell type and in the presence of hormonal contraceptives. The potential clinical implications of these findings should be further evaluated in vivo.